Magnetic Resonance Imaging of Human Glioma Cells by means of an Interleukin-6 Receptor-Targeted Contrast Agent

Authors

  • Alexander Sturzu,

    Corresponding author
    1. Department of Neuroradiology, University of Tübingen, Hoppe-Seyler-Str.3, 72076 Tübingen, Germany
    2. Peptide synthesis laboratory, Interfaculty Institute of Biochemistry, University of Tübingen, Hoppe-Seyler-Str.3, 72076 Tübingen, Germany
      * Corresponding authors: Alexander Sturzu, alexsturzu@yahoo.de and Stefan Heckl, stefan.heckl@med.uni-tuebingen.de
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  • Stefan Heckl

    Corresponding author
    1. Department of Neuroradiology, University of Tübingen, Hoppe-Seyler-Str.3, 72076 Tübingen, Germany
      * Corresponding authors: Alexander Sturzu, alexsturzu@yahoo.de and Stefan Heckl, stefan.heckl@med.uni-tuebingen.de
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* Corresponding authors: Alexander Sturzu, alexsturzu@yahoo.de and Stefan Heckl, stefan.heckl@med.uni-tuebingen.de

Abstract

The interleukin 6 receptor (IL-6R) and its ligand interleukin 6 (IL-6) play a crucial role in glioma growth and development accomplished by autocrine growth promotion and induction of angiogenesis via activation of vascular epithelial growth factor A (VEGF-A). Therefore, IL-6R represents a target for both therapy (preventing VEGF-A activation by blocking the receptor) and imaging (higher receptor density on tumor cells). A short heptapeptide that selectively binds to IL-6R and which inhibits the effect of IL-6 was coupled to the magnetic resonance imaging (MRI) contrast agent gadolinium (Gd)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) and the fluorescent dye rhodamine. MRI, confocal laser scanning microscopy, and flow cytometry showed that our IL-6-DOTA-rhodamine conjugate was taken up into the cytoplasm of human U373 glioma cells without any cytotoxic effects. Competition experiments indicate that this uptake was receptor-mediated. This conjugate might be used for future MRI studies of brain tumors after systemic or intraoperative local application. The cytoplasm specificity of the conjugate also makes it a potential building block for the design of future cytoplasm-directed imaging and therapeutic conjugates.

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